Lisocabtagene Maraleucel in R/R MCL: Primary Analysis Results from the MCL Cohort of the Single-Arm, Multicenter, Seamless Design TRANSCEND NHL 001 Study

Background

• Patients (pts) with R/R MCL after ≥2 prior lines of therapy, including Bruton tyrosine kinase inhibitor (BTKi), have a poor prognosis.
• Liso-cel is an autologous, CD19-directed, CAR T cell product administered at equal target doses of CD8+ and CD4+ CAR+ T cells.
• The phase 1, seamless design, dose-finding TRANSCEND NHL 001 study (NCT02631044) evaluated liso-cel in pts with R/R NHL. Here we report primary analysis results from the MCL cohort.

Methods

• Eligible pts had PET-positive R/R MCL after ≥2 lines of prior therapy, including a BTKi, alkylating agent, and CD20-targeted agent.
• Pts received liso-cel at a target dose level (DL) of 50 (DL1) or 100 × 106 CAR+ T cells (DL2) after lymphodepleting chemotherapy (LDC). Bridging therapy was allowed.
• Primary endpoints were treatment-emergent AEs (TEAEs) and ORR by IRC (Lugano 2014 criteria); secondary endpoints included CR rate (key), DOR, PFS, and OS.
• Primary (null hypothesis [H0]: ORR ≤40%) and key secondary (H0: CR rate ≤18%) efficacy hypothesis testing was hierarchical and based on the primary analysis set (PAS) of pts treated at DL2 with PET-positive disease per IRC at baseline (before LDC, after bridging therapy).
• The safety set included all pts who received liso-cel (DL1 + DL2). The efficacy set included all pts in the safety set who had PET-positive disease per IRC at baseline (DL1 + DL2).

Results

• At data cutoff (01/19/2023), of 104 leukapheresed pts, 88 received liso-cel (safety set; DL1, n = 6; DL2, n = 82).
• Median (range) age was 68.5 y (36–86), median (range) prior systemic lines of therapy was 3 (1–11), 69% had refractory disease, 53% were BTKi refractory, 33% had prior HSCT, 75% had Ki67 ≥30%, 31% had blastoid morphology, 23% had TP53 mutations, and 8% had active CNS disease.
• Median (range) on-study follow-up was 16.1 mo (0.4–60.5).
• The primary and key secondary endpoints were met based on the PAS (n = 74; ORR, 86.5% [95% CI, 76.5–93.3], P < 0.0001; CR rate, 74.3% [95% CI, 62.8–83.8], P < 0.0001).
• In the efficacy set (n = 83), ORR was 83.1% (95% CI, 73.3–90.5) with CR rate of 72.3% (95% CI, 61.4–81.6).
• Responses were durable: median DOR, 15.7 mo; median PFS, 15.3 mo.
• As most pts were enrolled during the COVID-19 pandemic and 6 pts in ongoing CR died due to COVID-19, DOR, PFS, and OS were also analyzed censoring for COVID-19 deaths.
• In the safety set (n = 88), 86% of pts had gr ≥3 TEAE, primarily cytopenias. Four gr 5 TEAEs occurred (3 related to liso-cel and/or LDC). Rate of any-grade cytokine release syndrome (CRS) was 61% (gr 3–4, 1%; no gr 5) and neurological events (NE) was 31% (gr 3–4, 9%; no gr 5). Rate of gr ≥3 infections was 15%, and prolonged cytopenia was 40%.

Conclusions

• Liso-cel demonstrated high ORR and CR rate that were durable and was well tolerated with low rates of gr ≥3 CRS, NE, and infections, thus representing a potential new treatment option for pts with high-risk, aggressive R/R MCL.

Wang M, Siddiqi T, Gordon LI, et al. Lisocabtagene maraleucel in R/R MCL: primary analysis results from the MCL cohort of the single-arm, multicenter, seamless design TRANSCEND NHL 001 study. Presented at: 17th International Conference on Malignant Lymphoma; June 13-17, 2023. Lugano, Switzerland.